Fat is an important nutrient the same as protein and saccharide and it is particularly useful as a high energy source. However, because fat is high in calories (9 kcal/g), it promotes obesity and is a cause for problems such as lifestyle-related illnesses. Actually, when hyperlipemia (hypercholesterolemia, hypertriglyceridemia) is found, a diet therapy is adopted as a first method of treatment and, when appropriate dietetic therapy and movement therapy are applied, the condition often improves and may become normalized. However, since fat enhances appetite, people today often eat foods containing large amounts of fat, and in advanced countries, where food is plentiful, excess fat intake is becoming a problem.
Most often, hypertriglyceridemia is a result of over eating, insufficient movement, obesity and excessive consumption of alcohol, and therefore, there are many cases where hypertension and diabetes mellitus occur as complications at the same time. Therefore, in many cases where there are multiple risk factors or where it is hard to improve daily lifestyle habits, in order to prevent the onset of ischemic heart diseases, a positive drug therapy is carried out.
With regard to drugs for hypertriglyceridemia, there are drugs of a fibrate type (in Japan, bezafibrate) (Bezatol SR® and Bezalip®) and fenofibrate (Lipantil®) are known as fibrate type drugs of the second generation. The main action of mechanism of the fibrate type drugs is mediated by activation of transcription factor α of an intranuclear receptor type (PPARα: peroxisome proliferator-activated receptor α).
Therefore, β-oxidation of fatty acid is promoted and production of hepatic triglyceride(s) lowers, and as a result, production of VLDL-TG is suppressed. In addition, activation of PPARα enhances an LPL activity and catabolism of triglyceride(s)-rich lipoprotein is accelerated. Further, an increase in the production of apo A I and A II and suppression of production of apo C III are induced. In addition, it has been noted that drugs of a fibrate type act to suppress cholesterol synthesis in the liver, promote sensitivity to insulin and promote discharge of cholesterol in bile. As a result, drugs of a fibrate type lower a triglyceride(s) concentration in serum by 20-50% and increase HDL-cholesterol by 10-15%.
As to other drugs, preparations of nicotinic acid (niceritrol (Perycit®) and nicomol (Cholexamin®)) have been found to be useful for hypertriglyceridemia and hyperglycemia of a mixed type (accompanied by hypertriglyceridemia, hypercholesterolemia and hypo-HDL-cholesterolemia). The main action mechanism of drugs of a nicotine type is that hepatic triglyceride(s) is lowered by inhibition of fatty acid synthesis, suppression of mobilization of fatty acid to the liver and suppression of esterification of hepatic fatty acid. At present, drugs of a fibrate type are used as the first choice, but in drug therapy, side effects such as hepatic function disorder, renal function disorder and myopathy must be noted. In addition, most side effects of drugs are expressed within six months after initiation of administration, and therefore, it is important to watch for the onset of side effects when the effectiveness of the drug is tested during the period of six months or, at least three to four months, after the administration is started or the dosage is increased. Accordingly, very careful attention is necessary during the administration of drugs, and it is not possible to administer such drugs for the purpose of prevention.
At present, as a preventive means, development of substitutes for fat/oil and non-absorbing fat/oil has been carried out, an example being sucrose fatty acid polyester (U.S. Pat. No. 3,600,186). Since it is discharged without being absorbed in vivo, the amount of calories derived from fat/oil is 0 kcal/g. However, absorption of fat-soluble vitamins is inhibited, and essential fatty acids are not supplied, and therefore, it is unable to be used as a commonly-used fat/oil. Under the circumstances, diacylglyceride has been developed in recent years as a source for supplying essential fatty acids.
In diacylglyceride, fatty acids are bonded mostly to 1,3-positions of a triglyceride(s), and upon being absorbed, fatty acids are cut out by a pancreatic lipase which is specific to 1,3-positions and the resulting glyceride and fatty acids are absorbed from the intestine. However, they are not reconstructed to a triglyceride(s) in epidermal cells of the small intestine but are absorbed with the portal vein and carried to the liver directly. Accordingly, accumulation of fat is suppressed. (In the case of a triglyceride(s), 2-acylmonoglyceride and fatty acid are absorbed in the intestine, reconstructed to a triglyceride(s) in epidermal cells of the small intestine, incorporated with chylomicron, secreted into lymph and circulate through the peripheral tissues.)
However, none of the developed fat/oil substitutes have the effect of drugs to burn fat in vivo (β-oxidation) and the effect is limited as well. Although inhibitors for pancreatic lipase to suppress absorption have been developed as well, their effect is also limited.